A5053708779- RNA and protein synthesis mechanisms
- RNA Research and Splicing
- RNA modifications and cancer
- DNA and Nucleic Acid Chemistry
- Protein Structure and Dynamics
- MicroRNA in disease regulation
- Genetic and Kidney Cyst Diseases
- Advanced NMR Techniques and Applications
- Chemical Synthesis and Analysis
- Renal and related cancers
- Helicobacter pylori-related gastroenterology studies
- HIV/AIDS drug development and treatment
- Enzyme Structure and Function
- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Advanced biosensing and bioanalysis techniques
- HIV Research and Treatment
- Monoclonal and Polyclonal Antibodies Research
- Viral gastroenteritis research and epidemiology
- Molecular spectroscopy and chirality
- Galectins and Cancer Biology
- Biomedical Research and Pathophysiology
- Bacteriophages and microbial interactions
- Computational Drug Discovery Methods
- Glycosylation and Glycoproteins Research
Karolinska Institutet
2015-2024
Uppsala University
2023-2024
Science for Life Laboratory
2024
Stellenbosch University
2022
Swiss Integrative Center for Human Health
2012-2017
University of Zurich
2013-2017
Marqués de Valdecilla University Hospital
2014
Ludwig-Maximilians-Universität München
2014
Leipzig University
2013
University of Michigan–Ann Arbor
2011-2013
Klotho and fibroblast growth factor 23 (FGF23) are key regulators of mineral metabolism in renal insufficiency. FGF23 levels have been shown to increase early chronic kidney disease (CKD); however, the corresponding soluble at different CKD stages not known. Soluble Klotho, FGF23, parathyroid hormone (PTH), 1,25-dihydroxy vitamin D3 (1,25D) other parameters were measured an observational cross-sectional study 87 patients. Locally weighted scatter plot smoothing function these plotted versus...
Autosomal dominant polycystic kidney disease (ADPKD) is the fourth most common renal requiring replacement therapy (RRT). Still, there are few epidemiological data on prevalence of, and survival RRT for ADPKD. This study used from ERA-EDTA Registry in 12 European countries with 208 million inhabitants. We studied four 5-year periods (1991–2010). Survival analysis was performed by Kaplan–Meier method Cox proportional hazards regression. From first to last period, of ADPKD increased 56.8 91.1...
Abstract The current pandemic situation caused by the Betacoronavirus SARS-CoV-2 (SCoV2) highlights need for coordinated research to combat COVID-19. A particularly important aspect is development of medication. In addition viral proteins, structured RNA elements represent a potent alternative as drug targets. search drugs that target requires their high-resolution structural characterization. Using nuclear magnetic resonance (NMR) spectroscopy, worldwide consortium NMR researchers aims...
Helicobacter pylori can cause peptic ulcer disease and/or gastric cancer. Adhesion of bacteria to the stomach mucosa is an important contributor vigour infection and resulting virulence. H. adheres primarily via binding BabA adhesins ABO/Lewis b (Leb) blood group antigens SabA sialyl-Lewis x/a (sLex/a) antigens. Similar most Gram-negative bacteria, continuously buds off vesicles derived from pathogenic often include virulence-associated factors. Here we biochemically characterized highly...
Reduced kidney function is a risk factor for hyperuricaemia and gout, but limited information on the burden of gout available from studies patients with chronic disease (CKD). We therefore examined prevalence correlates in large prospective observational German Chronic Kidney Disease (GCKD) study.Data 5085 CKD aged 18-74 years an estimated glomerular filtration rate (eGFR) 30-<60 mL/min/1.73 m(2) or eGFR ≥60 overt proteinuria at recruitment non-missing values self-reported medications urate...
NMR spectroscopy is uniquely suited for atomic resolution studies of biomolecules such as proteins, nucleic acids and metabolites, since detailed information on structure dynamics are encoded in positions line shapes peaks spectra. Unfortunately, accurate determination these parameters often complicated time consuming, part due to the need different software at various analysis steps validating results. Here, we present an integrated, cross-platform open-source that significantly more...
Liquid–liquid phase separation (LLPS) of heterogeneous ribonucleoproteins (hnRNPs) drives the formation membraneless organelles, but structural information about their assembled states is still lacking. Here, we address this challenge through a combination protein engineering, native ion mobility mass spectrometry, and molecular dynamics simulations. We used an LLPS-compatible spider silk domain pH changes to control self-assembly hnRNPs FUS, TDP-43, hCPEB3, which are implicated in...
Estimates of intramolecular distances are essential for structure determination (see figure). For medium-sized molecules, ROESY NMR spectroscopy is the method choice obtaining distances. However, integration cross-peaks problematic, owing to offset dependence integrals and/or TOCSY artefacts. We here present EASY (Efficient Adiabatic SYmmetrized ROESY), which yields reliable without a sample-specific setup.
Background In autosomal dominant polycystic kidney disease (ADPKD), total volume (TKV) is regarded as an important biomarker of progression and different methods are available to assess volume. The purpose this study was identify the most efficient computation method be used in clinical studies evaluating effectiveness treatments on ADPKD progression. Methods findings We measured single (SKV) two series MR CT images from (experimental dataset) by independent operators (expert beginner),...
Gaining insight into the uptake, trafficking and target engagement of drugs in cells can enhance understanding a drug's function efficiency. However, there are currently no reliable methods for studying untagged biomolecules macromolecular complexes intact human cells. Here we have studied an antisense oligonucleotide (ASO) drug HEK 293T HeLa by NMR spectroscopy. Using combination transfection, cryoprotection dynamic nuclear polarization (DNP), were able to detect directly frozen Activity...
Abstract The knowledge of structure and dynamics is crucial to explain the function RNAs. While nuclear magnetic resonance (NMR) well suited probe these for complex biomolecules, it requires expensive, isotopically labeled samples, long measurement times. Here we present SELOPE, a new robust, proton‐only NMR method that allows us obtain site‐specific overview in an entire RNA molecule using unlabeled sample. SELOPE simplifies assignment cost‐effective screening response nucleic acids...
Approaches that combine experimental data and computational molecular dynamics (MD) to determine atomic resolution ensembles of biomolecules require the measurement abundant data. NMR residual dipolar couplings (RDCs) carry rich information, however, difficulties in modulating overall alignment nucleic acids have limited ability fully extract this information. We present a strategy for RNA is based on introducing variable dynamic kinks terminal helices. With strategy, we measured seven sets...
Background Autosomal dominant polycystic kidney disease (ADPKD) is characterized by a decline in renal function at late stage when the majority of functional parenchyma replaced cystic tissue. Thus, function, assessed estimated glomerular filtration rate (eGFR) does not well represent burden early disease. Here, we investigated various urinary markers for tubular injury and their association with ADPKD patients course. Methods between 18 40 years an eGFR greater or equal to 70 ml per min...
Abstract Changes in molecular structure are essential for the function of biomolecules. Characterization these structural fluctuations can illuminate alternative states and help correlating to function. NMR relaxation dispersion (RD) is currently only method detecting alternative, high‐energy states. In this study, we present a versatile 1 H R 1ρ RD experiment that not extends exchange timescales at least three times beyond rate limits 13 C/ 15 N ten CPMG experiments, but also makes use...
Recent findings in genome-wide transcriptomics revealed that RNAs are involved almost every biological process, across all domains of life. The characterization native unknown function and structure is particularly challenging due to their typical low abundance the cell inherent sensitivity toward ubiquitous RNA degrading enzymes. Therefore, robust vitro synthesis extensive work-up methods often needed obtain samples amenable for biochemical, biophysical, structural studies. Here, we present...
ABSTRACT microRNAs (miRNAs) regulate target mRNA expression post-transcriptionally through their association with Argonaute 2 (AGO2) proteins. Predicting the efficiency of repression by miRNA has been limited our comprehension structure-function relationship within binding sites. Using a combination EMSA, luciferase reporter assays, and structural probing, we investigated interaction between human tumour suppressor miR-34a 12 targets. Comparison direct RNA:RNA interactions those functional...